An intrinsic diffusion response function for analyzing diffusion functional MRI time series
Abstract
To disentangle the temporal profiles of the diffusion and BOLD components of diffusion-weighted functional MRI (DfMRI) during visual activation, we extracted the raw signal from an anatomically defined volume of interest encompassing the visual cortex of 16 subjects. Under the assumption of a linear, time invariant system we were able to define an intrinsic diffusion response function (DRF) from neural tissue, as a counterpart to the hemodynamic response function (HRF) commonly used in BOLD-fMRI. The shape of the DRF response was found to be very similar to the time courses of optical imaging transmittance signals, thought to originate from local geometric changes in brain tissue at the microscopic scale. The overall DfMRI signal response was modeled as the convolution of the stimulation paradigm time course with a DhRF, which is the sum of the DRF and a fractional HRF resulting from residual tissue T2-BOLD contrast. The contribution of the HRF to the DfMRI signal was found to be 26% at peak amplitude, but the DRF component which has a much steeper onset contributed solely at beginning of the response onset. The suitability of this model over the canonical HRF to process DfMRI data was then demonstrated on datasets acquired in 5 other subjects using a rapid event-related design. Some non-linearities in the responses were observed, mainly after the end of the stimulation.
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T2-weighted spin-echo diffusion MRI retains residual vascular effects related to BOLD.
“T2-weighted spin-echo diffusion MRI retains residual vascular effects related to BOLD (Aso et al., 2009; de Riedmatten, Spencer, Olszowy, et al., 2025; Kershaw et al., 2009; Miller et al., 2007).”
From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Aso et al., 2009
T2-related effects are largely independent of b-value, so that, when echo time is matched, their contributions can be substantially reduced or eliminated by calculating an ADC or sADC derived from two b-values.
“T2-related effects (which are weaker than T2*-weighted BOLD) are largely independent of b-value, so that, when echo time is matched, their contributions can be substantially reduced or eliminated by calculating an ADC or, better, sADC derived from two b-values (Aso et al., 2009; de Riedmatten, Spencer, Olszowy, et al., 2025; Le Bihan et al., 2006; Spencer et al., 2025).”
From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Aso et al., 2009
Once confounds are carefully controlled, an intrinsic diffusion response function should be used in place of the canonical hemodynamic response function used in BOLD fMRI.
“Once these confounds are carefully controlled, an intrinsic diffusion response function should be used in place of the canonical hemodynamic response function used in BOLD fMRI (Aso et al., 2009).”
From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Aso et al., 2009
Cites
Imaging cell volume changes and neuronal excitation in the hippocampal slice
Andrew, R. D., & Macvicar, B. A. (1994) · Neuroscience · doi:10.1016/0306-4522(94)90372-7 · Cited by 304 · see citing works
Direct and fast detection of neuronal activation in the human brain with diffusion MRI
Le Bihan, D., Urayama, S.-I., Aso, T., Hanakawa, T., & Fukuyama, H. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600644103 · Cited by 272 · see citing works
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Functional diffusion tensor imaging at 3 Tesla
Mandl, R. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00817 · Cited by 18 · see citing works
40 Years of diffusion MRI in the brain: From history to emerging frontiers
Le Bihan, D. (2026) · Imaging Neuroscience · doi:10.1162/imag.a.1365
“T2-weighted spin-echo diffusion MRI retains residual vascular effects related to BOLD ( Aso et al., 2009; de Riedmatten, Spencer, Olszowy, et al., 2025; Kershaw et al., 2009; Miller et al., 2007).”
- Authors
- Aso, T., Urayama, S.-I., Poupon, C., Sawamoto, N., Fukuyama, H., & Bihan, D. L.
- Affiliations
- Kyoto University (JP)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Corresponding author
- Aso, Toshihiko
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 47
- Issue
- 4
- Pages
- 1487-1495
- ISSN
- 1053-8119 (ISSN-L)
- OpenAlex
- W1994857646
- Cited by
- 47
- References
- 2
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 2 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 1 · 2015: 4 · 2014: 4 · 2013: 5 · 2012: 4
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (21613004)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Keywords
- hemodynamic response function, visual cortex activation, BOLD signal, visual stimulation, linear time-invariant systems, event-related design
- MeSH terms
- Adolescent, Adult, Algorithms, Evoked Potentials, Visual, Female, Humans, Image Enhancement, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Sensitivity and Specificity, Visual Cortex, Reproducibility of Results, Diffusion Magnetic Resonance Imaging, Young Adult
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